The overall objective of the present project is to characterize intrinsic cellular mechanisms or events that govern the contractile response of vascular smooth muscle and the possible modification of these systems in hypertensive vascular disease. Ionized calcium levels of the smooth muscle cytoplasm represent a major determinant of the contractile response. The present study is focused on the metabolic regulation of calcium in vascular smooth muscle and in related systems that may shed light on the vascular smooth muscle. Detailed studies of the metabolic regulation of calcium in vascular muscle of the SHR (spontaneously hypertensive Wistar-Kyoto) rat are to be carried out. Possible relationships between vascular reactivity, hypertensive disease and intracellular systems regulating calcium are to be looked for. Specific characterization of calcium regulating activity in plasma membrane of vascular smooth muscle is to be attempted since this is the frequent site of hormone and drug interactions. The pig coronary artery is to be studied as a model system. Investigations into the interaction of calcium nucleotides and prostaglandins are to be initiated. BIBLIOGRAPHIC REFERENCES: Effect of parathion and its metabolites on calcium uptake activity of rat skeletal muscle sarcoplasmic reticulum in vitro. N. Binder, E.J. Landon, L. Wecker and W.D. Dettbarn. Biochem. Pharm. 25, 835-839 (1976). Characterization of calcium regulating systems in smooth muscle membranes. E.J. Landon, F. Wuytack, S. Fox, Fed. Proc. 35, 436 (1976).